Recent improvements in the treatment results of patients with childhood leukemia have resulted from a careful assessment of the failure risk based on many variables linking to the prognosis, such as initial leukocyte count, age at diagnosis, and cytogenetic abnormalities (risk factors), and also from the development of risk-directed therapy. In acute lymphoblastic leukemia (ALL), however, the stratification of patients by conventional risk factors is inadequate ; relapses occur in about 15% of low-risk cases, and some cases with t (9 ; 22), which is extreme high-risk characteristics, can be cured with chemotherapy alone. Recent reports suggest that poor early response to therapy and the presence of minimal residual disease (MRD) during the post-remission-induction period are reliable indicators of a poor prognosis. Patients with>1, 000 leukemic blasts/μl on day 8 of induction show a significantly poor outcome. The MRD at a level of 10^-2 or more at the end of induction is a strong adverse risk factor of relapse. These factors can greatly improve the accuracy of risk assessment and thus contribute to the decision making of optimal treatment intensity. In acute myelogenous leukemia (AML), the cytogenetic features have been proved to be the most important prognostic factor. Patients with t (8 ; 21) or inv (16) are cured with chemotherapy alone, which can reduce long-term complications associated with highly intensive therapy including stem cell transplantation. Further studies on leukemic cells of individual patients, such as drug sensitivity, genetic polymorphism and pharmacokinetics, and distinct gene expression detected by DNA microarray, will lead to more accurate patient stratification, which prevents both over-and undertreatment.

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Oral 6-mercaptopurine (6-MP) is an integral component of maintenance chemotherapy for children with acute lymphoblastic leukemia (ALL). A clinical comparative study of 6-MP given at 175 mg/m²/day vs. 250 mg/m²/day for 5 days was carried out. Ten patients on a CCLSG ALL 874 and 911 study received 6-MP at 175 mg/m²/day and 9 patients on a CCLSG ALL 941 study received 6-MP at 250 mg/m²/day. There was no significant difference in the value of WBC, Hb, and platelet counts between these two groups. The mean value of GPT level was significantly increased in a higher dosage group with no delay of 6-MP administration. The mean value of GPT peak level was decreased gradually following repeated cycles of 6-MP administration. Five days of 6-MP at 250 mg/m²/day was well tolerated and safe for the maintenance chemotherapy of childhood ALL.

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The growth of childhood acute lymphoblastic leukemia (ALL) was studied in 215 patients (140 boys and 75 girls) who had remained in remission for more than a year after the completion of their maintenance therapy. The median age at diagnosis was 4.2 years, and the median duration of follow-up from the time of diagnosis was 6.0 years. The children had been treated by ALL-protocol of the Children's Cancer and Leukemia Study Group. Heights and weights were examined at diagnoses up to 10 years after the cessation of chemotherapy. The Z score, which reflects the deviation of height and weight measurements from the population mean, was used to assess height and weight changes. The mean height Z score was-0.36 SD at the cessation of chemotherapy and-0.59 SD at 5 years. Seven years after the cessation of chemotherapy, the girls showed a decrease in the mean height Z score (-1.32 SD) compared with the boys (0.16 SD) (p<0.01). The mean weight Z score was 0.36 SD at the cessation of chemotherapy and-0.36 SD at 5 years. Obesity was seen in 7.9% at the cessation of chemotherapy. No obvious correlation between the administered cranial irradiation and growth failure was found. The short stature seen in patients treated for ALL is more pronounced in girls than in boys.

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We studied the safety and efficacy of melphalan (L-PAM) and/or total body irradiation administered as the preconditioning for hematopoietic stem cell transplantation (HSCT) in 15 patients with pediatric cancer in an open trial design. Engraftment was achieved in all patients, and the median time of engraftment was 16 days. Of the 5 patients with evaluable disease, 1 was in complete remission (CR), 1 was in very good partial remission (VGPR), 1 was in partial remission (PR), and 2 showed no change (NC); the efficacy rate was 60.0%. Regarding safety, side effects occurred in all 15 patients. The major symptoms : diarrhea (86.7%); stomatitis·mucositis (80.0%); transient increases of GOT and GPT (66.7%); and nausea and vomiting (53.3%). Definite and suspected infections occurred in 13 patients (86.7%). No transplant-related deaths or serious adverse events occurred. In all, 4 patients died. The causes of the death were disseminated intravascular coagulopathy (DIC) as a result of sepsis in 1 patient and recurrent cancer in 3. Of 7 patients who received allogeneic bone marrow transplantation, 3 had acute graft-versus-host disease (GVHD), assessed as grade I. However, no chronic GVHD was observed at the 2-year follow-up. Overall survival at 3 years (median, 1, 135 days) was 71.4%. These findings suggest that L-PAM is effective as a preconditioning for HSCT in pediatric cancer with an acceptable safety profile.

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Graft failure is a serious and often life-threatening complication of allogeneic stem cell transplantation (SCT). A second SCT with intensified immunosuppression is the main therapeutic option. However, primary graft failure without autoreconstitution after unrelated SCT or cord blood transplantation (CBT) is often an urgent issue because of a high risk of infection and the difficulty of an early retransplantation from original donors. In this study, we analyzed the outcome of retransplantation following graft failure. From 1995 to 2000, 7 patients with graft failure were retransplanted. Five had nonmalignant disorders, including 1 multiply transfused patient with severe aplastic anemia. Six patients had primary graft failure and 1 had secondary graft failure. Four patients with graft failure after related SCTs were retransplanted from the same donors. Three with graft failure after unrelated SCTs (including 2 CBTs) were retransplanted from HLA-2-or-3-mismatched related donors, 2 of whom received positively selected CD34⁺ blood cells. Conditioning regimens for the second transplant were intensified by using total body irradiation (TBI) or fludarabine. All except 1 patient, who had been alloimmunized by multiple transfusions, had a successful engraftment following the second transplant. In conclusion : 1) graft failures were successfully treated with retransplantation; 2) TBI and fludarabine are effective for immunosuppression in retransplantation ; and 3) retransplantation of positively selected CD34+ cells from HLA-mismatched related donors is a useful treatment for graft failure following unrelated SCT.

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We report a 15-year-old boy who developed a rapidly progressive and fatal Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after bone marrow transplantation. He underwent an unrelated bone marrow transplantation from a genotypically HLA 2-locus mismatched donor for acute lymphocytic leukemia in third complete remission. A conditioning regimen included antithymocyte globulin. He developed fungal septicemia on day 59 and acute graft-versus-host disease (GVHD) of the skin on day 68, followed by hepatosplenomegaly and edema in the face and the extremities. He presented with cervical swelling and dyspnea as a result of edema of the larynx on day 75 and was diagnosed with having monoclonal LPD. Prednisolone could not be discontinued because of the progression of acute GVHD. Acyclovir, large doses of intravenous immunoglobulin, and donor lymphocyte transfusion were not effective, and he died of septicemia on day 92. An autopsy specimen revealed extensive infiltration of lymphoma cells in multiple organs. Since monoclonal LPD can be rapidly progressive and fatal as in the present case, a monitoring of EBV genome in peripheral blood is indispensable for an early diagnosis and treatment in the LPD high-risk group.

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We encountered a 12-year-old boy with vitamin B₁₂-deficient megaloblastic anemia complicated with generalized pigmentation. The patient was administered vitamin B₁₂ subcutaneously, and his anemia improved in approximately eight months. His skin pigmentation also improved gradually, and it almost completely disappeared in the course of three years. This patient experienced no other complications such as autoimmune or endocrine disorders ; therefore his pigmentation is considered to be due to vitamin B₁₂ deficiency. Pigmentation is an extremely rare complication of vitamin B₁₂-deficient megaloblastic anemia, and is not described even in textbooks. However, a diagnosis of vitamin B₁₂-deficient megaloblastic anemia should be considered in patients showing pigmentation, especially those who complain of easy fatigability, and a blood examination should be performed at an early stage of the disease.

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An 11-year-old boy was admitted to our hospital because of a tumor in the left inguinal region that measured 6 cm in diameter. MRI and gallium scintigraphy revealed a swelling of the intraperitoneal lymph node, but the supra diaphragmatic region has no evidence of swelling. He had no B symptoms, such as fever, drenching sweats, or weight loss. A histologic examination of the tumor revealed Hodgkin's disease, nodular sclerosis. In Japan, Hodgkin's disease in childhood originating from an inguinal lymph node is very rare.

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Chemotherapy is the standard treatment for advanced-stage Hodgkin's disease (HD) and a therapeutic alternative for early-stage disease. However, optimal therapy for children with HD is controversial. In this study, 7 patients (6 previously untreated and 1 with relapse) aged 3 to 13 years with HD treated in our institution from 1984 to 2000 were evaluated retrospectively. All patients were treated with combination chemotherapy, which consisted of cyclophosphamide, vincristine, procarbazine, and prednisolone (COPP) in 2 patients, both COPP and pirarubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in 1, and ABVD in 4. Two patients who received COPP and the 1 patient with relapse had added radiotherapy. Two patients developed severe infection (herpes zoster and CMV pneumonia) during COPP, but no patients developed severe myelotoxicity during ABVD. During a follow-up period of 9-205 months, all patients were alive without disease. No patient has developed a second malignancy, hypothyroidism, or hypogonadism. Based on our small number of patients, we concluded that ABVD without radiotherapy is effective and safe in the treatment of HD. However, the study of more patients and further follow-up are needed.

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We report a 43-day-old Bangladesh boy with Hb E disease, early diagnosed by gene analysis. Microcytic hypochromic anemia became severe (MCV 74.0 fl, MCH 24.9 pg) even after his recovery from sepsis, and a blood transfusion was inevitable. Microcytic hypochromia at his birth and his mother's same anemia suggested hereditary Hb abnormality. The 26th codon of the chain was found to be AAG (Lys) instead of GAG (Glu) by a gene analysis of the gene of his beta-globin chain. His mother also had the same abnormal hemoglobinopathy. Hb E disease is popular in Southeast Asia. Foreigners from Southeast Asia has been increasing recently in Japan. Gene analysis is a useful tool to diagnose this disease.

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We reported a case of an infant with acute myelomonocytic leukemia (AMMoL) developing leukemic invasion of the anterior chambers. A 5-month-old girl was admitted to our hospital because of symptoms similar to those of an upper respiratory infection. We diagnosed her as suffering from AMMoL by bone marrow aspiration. Induction therapy failed to achieve a remission. She developed hypopyon in both eyes, and the diagnosis of leukemic invasion was confirmed with anterior chamber paracentesis. Hypopyon was controled well by radiation to the eyes. She did not develop a CNS leukemia other than anterior chamber involvement. She received stem cell transplantation two times. Peripheral stem cells were obtained from her haplotype-matched father by using CD34 positivity. Remission, however, was not achieved. Four days after the second transplantation, she died from acute renal failure and hepatic insufficiency probably a result of thrombotic microangiopathy. Hypopyon in AMMOL is rarely seen. Infants undergoing antileukemic therapy should have regular examinations by an ophthalmologist.

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